H₂-receptor antagonist



  An H2-receptor antagonist, (H2RA) often shortened to H2 antagonist, is a drug used to block the action of proton pump inhibitors.

Like the receptor antagonists.

History and development

antagonist to suppress stomach acid secretion.

In 1964 it was known that antihistamines had no effect on acid production. From these facts the SK&F scientists postulated the existence of two histamine receptors. They designated the one acted on by the traditional antihistamines H1, and the one acted on by histamine to stimulate the secretion of stomach acid H2.

The SK&F team used a rational drug design process starting from the structure of histamine - the only design lead, since nothing was known of the then hypothetical H2 receptor. Hundreds of modified compounds were synthesised in an effort to develop a model of the receptor. The first breakthrough was Nα-guanylhistamine, a partial H2-receptor antagonist. From this lead the receptor model was further refined and eventually led to the development of competitive antagonist at the H2 receptor 100-times more potent than Nα-guanylhistamine, proved the existence of the H2 receptor.

Burimamide was still insufficiently potent for oral administration and further modification of the structure, based on modifying the Cimetidine (common brand name Tagamet).

GlaxoSmithKline) in an effort to match the success of Smith, Kline & French with cimetidine. Ranitidine was also the result of a rational drug design process utilising the by-then-fairly-refined model of the histamine H2 receptor and quantitative structure-activity relationships (QSAR).

Glaxo refined the model further by replacing the adverse drug reactions), longer-lasting action, and ten times the activity of cimetidine.

Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug by 1988. The H2-receptor antagonists have since largely been superseded by the even more effective omeprazole becoming the biggest-selling drug for many years.

Pharmacology

The H2 antagonists are competitive inhibitors of acetylcholine) have a reduced effect on parietal cells when the H2 receptors are blocked.

Clinical use of H2-antagonists

Indications

H2-Antagonists are clinically used in the treatment of acid-related Gastrointestinal conditions. Specifically, these indications may include:[1]

  • Peptic Ulcer Disease (PUD)
  • Gastroesophageal Reflux Disease (GERD)
  • Dyspepsia
  • Stress Ulcer Prophylaxis (Ranitidine)

People that suffer from heartburn (GERD) infrequently may take either Proton pump inhibitors, however, are the preferred treatment for Erosive Esophagitis since they have been shown to promote healing better than H2-antagonists.

Some studies also suggest that H2-antagonists might be effective in treating herpes viruses, such as shingles and herpes simplex [1].

Adverse drug reactions

H2 antagonists are generally well-tolerated, except for adverse drug reactions (ADRs) are common. Infrequent ADRs include hypotension. Rare ADRs include: headache, tiredness, dizziness, confusion, diarrhoea, constipation, and rash.[1] Additionally, cimetidine may also cause gynecomastia in males, loss of libido, and impotence, which are reversible upon discontinuation.

Drug interactions

With regard to MDMA.

The more recently developed H2-receptor antagonists, such as famotidine, are much less likely to alter CYP metabolism.[2]

Examples

Cimetidine was the prototypical member of the H2 antagonists. Further developments, using quantitative structure-activity relationships (QSAR) led to the development of further agents with improved tolerability-profiles. In the United States, all four members of the group are available over the counter in relatively low doses, and have become extremely popular medications marketed to heartburn sufferers.

References

  1. ^ a b Rossi S (Ed.) (2005). Australian Medicines Handbook 2005. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-9-3
  2. ^ Review article: drug interactions with agents used to treat acid-related diseases, Alimentary Pharmacology & Therapeutics 13 (s3), 18–26, http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-2036.1999.00021.x
  • Katzung, Bertram G. (2004). Basic and Clinical Pharmacology, 9th ed. ISBN 0-07-141092-9
v • d • e
Antihistamines
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Drugs for acid related disorders: Drugs for peptic ulcer and GERD/GORD (Pirenzepine
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NMDA antagonist
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "H₂-receptor_antagonist". A list of authors is available in Wikipedia.